Brain Markers Could Yield Early Clues into Parkinson’s Disease

Parkinson’s disease affects over 1.1 million people in the United States, progressively damaging the brain cells that control movement. By the time symptoms like tremors appear, patients have already lost around half of the affected brain cells, making early detection crucial.

Now, a new study in Movement Disorders uses brain imaging to reveal how Parkinson's disease disrupts the normal relationship between two important neural indicators.

Researchers used positron emission tomography, or PET, to measure two markers in patients' brains: dopamine transporters—proteins that are responsible for uptake of the neurotransmitter dopamine, an important chemical implicated in the disease—and synaptic density, which reflects the overall health and number of connections between brain cells.

In healthy participants, these two markers rise and fall together in a predictable pattern within the striatum, the brain region most affected by Parkinson's disease. But in patients affected by the disease, this relationship breaks down, the researchers found.

"Our findings suggest that Parkinson's pathology alters the correlation between dopamine transporter availability and synaptic density," says study co-author Tommaso Volpi, MD, PhD, a postdoctoral associate in the Department of Radiology and Biomedical Imaging at Yale School of Medicine (YSM).

One challenge to early diagnosis of Parkinson's disease is that symptoms like tremor and rigidity can overlap with other similar conditions.

“Existing dopamine imaging techniques are generally reliable, though they can sometimes miss early changes. That’s why in our study, we looked at how different brain markers relate to one another to give a more complete picture of what’s happening in Parkinson’s disease,” says co-author Faranak Ebrahimian Sadabad, MD, a postdoctoral associate at the Yale NeuroPET Imaging Program. “Instead of relying on a single measurement, we wanted to understand how these signals work together, especially in different stages.”

The study included 30 patients with Parkinson’s disease and 13 healthy volunteers, and each person underwent two separate PET scans. The first scan used a special tracer to measure dopamine transporters, which served as a measure of dopamine neurons; the second used a different tracer to measure synaptic density.

The team then compared these two measurements in the brain regions most affected by Parkinson's disease, looking for differences between healthy people and patients at various stages of the disease.

“In healthy brains, we saw a strong correlation between dopamine neuron density and synaptic density,” says senior author David Matuskey, MD (pictured above), associate professor of radiology and biomedical imaging, of psychiatry, and of neurology at YSM. “In Parkinson's disease, that relationship deteriorated, and that to me is the heart of our study.”

In the patients with Parkinson’s disease, researchers observed that dopamine neuron loss was higher than synaptic loss.

“And we saw changes becoming more pronounced in more advanced disease stages,” says Volpi.

By combining multiple imaging markers, researchers can get a clearer, more detailed picture of Parkinson’s disease than any single test could provide, the authors say. And the team hopes to use these measures to develop biomarkers that could reveal how the disease unfolds over time.

“Understanding how dopamine loss and the breakdown of brain connections overlap, or don’t, over time could shed light on why Parkinson’s disease progresses the way it does,” says Volpi. “These insights could also help researchers zero in on the biological mechanisms driving the disease, which are still somewhat elusive.”